The kidney contains several distinct epithelia that, in their aggregate function, are responsible for formation of the urine and the maintenance of fluid and electrolyte homeostasis. We are studying the roles of these epithelia in the regulation of the excretion of water, urea, sodium, and chloride. The central approach is to microdissect the epithelia from the kidney and to study their functions in vitro. These studies measure the transport by the epithelia, the level of expression of various transport proteins in renal tubules, intracellular signalling in individual renal tubule segments, and the levels of nucleic acids (mRNA) for proteins that are involved in the regulation of both the transport and metabolic functions of the epithelia. The data are analyzed and integrated using mathematical models of transport in the kidney. The current focus is on: 1) the mechanism of action of vasopressin in the regulation of water channel and urea carrier function in the renal collecting duct; 2) the molecular physiology of the urinary concentrating mechanism; 3)development and characterization of polyclonal antibodies against renal medullary transport proteins; 4) molecular physiology of renal NaCl transport regulation.